The H-2 linked I region codes for genes which control immune response, genes, immune suppression genes, lymphocyte activating determinants, histocompatibility antigens, and finally, a set of lymphocyte antigens designated as Ia. The Ia antigens, which are serologically defined, have been a boon in elucidating and characterizing the I region products. Due to the similarity in the organization of the major histocompatibility complex between the mouse and the human system, the I region of the mouse has served as a model for immune response genes in the human. Our long-range objectives of this proposed research is thorough characterization of the Ia antigens such that they can serve as a useful tool in the elucidation of the organization, function and regulation of the multiple genes which map in this chromosomal segment. 1. Serologic characterization. All known H-2 haplotypes of inbred strains and wild strains will be further serologically analyzed to get a complete picture of the Ia antigen distribution, and further immunizations will be done to produce monoregional and monospecific antisera. 2. Genetic organization. Old and new H-2 recombinants and mutants will be analyzed to further understand the number of loci mapping within this region and the interactions of the genes which control the different immune phenomena. 3. Tissue distribution. Further characterization of Ia antigens on lymphocytes and non-lymphoid cells will be pursued. Among the lymphocytes, particular attention will be given to the study of Ia antigens on thymocytes, T cell leukemias, and macrophages. 4. Chemical characterization. In collaboration with Dr. Susan Cullen, studies will be pursued to further characterize Ia molecules expressed on different cell types. BIBLIOGRAPHIC REFERENCES: David, C. S. Major Histocompatibility Complex of the Mouse. In: "Organization of Major Histocompatibility Systems in Animals", Ed. D. Gotze, Springer-Verlaag, 1977, in press. Schwartz, B. D., A. M. Kask, S. O. Sharrow, C. S. David, and R. H. Schwartz. Partial chemical characterization of Ia antigens derived from murine thymus T cells. Proc. Natl. Acad. Sci., 1977, in press.